Skip to main content
NCBI home page
Journal of Cellular and Molecular Medicine logoLink to Journal of Cellular and Molecular Medicine
. 2007 May 1;5(1):18–32. doi: 10.1111/j.1582-4934.2001.tb00135.x

Contribution of apoptotic cell death to renal injury

Alberto Ortiz 1,✉, Corina Lorz 1, Pilar Justo 1, Marina P Catalán 1, Jesüs Egido 1
PMCID: PMC6737749  PMID: 12067448

Abstract

Cell number abnormalities are frequent in renal diseases, and range from the hypercellularity of postinfectious glomerulonephritis to the cell depletion of chronic renal atrophy. Recent research has shown that apoptosis and its regulatory mechanisms contribute to cell number regulation in the kidney. The role of apoptosis ranges from induction to repair and progression of renal injury. Death ligands and receptors, such as TNF and FasL, proapoptotic and antiapoptotic Bcl‐2 family members and caspases have all been shown to participate in apoptosis regulation in the course of renal injury. These proteins represent potential therapeutic targets, which should be further explored.

Keywords: apoptosis, kidney, acute renal failure, glomerulonephritis, Bcl‐2, death receptor, caspase

References

  • 1. Ortiz A. Apoptotic regulatory proteins in renal injury. Kidney Int 58: 467, 2000. [DOI] [PubMed] [Google Scholar]
  • 2. Vaux D.L., Korsmeyer S.J. Cell death in development. Cell 96:245, 1999. [DOI] [PubMed] [Google Scholar]
  • 3. Green D.R. Apoptotic pathways: the roads to run. Cell 94:695, 1998. [DOI] [PubMed] [Google Scholar]
  • 4. Ashkenazi A., Dixit V.M. Death receptors: signaling and modulation. Science 281:1305, 1998. [DOI] [PubMed] [Google Scholar]
  • 5. Adams J.M., Cory S. Life‐or‐death decisions by the Bcl‐2 protein family. Trends Biochem Sci 26:61, 2001. [DOI] [PubMed] [Google Scholar]
  • 6. Thornberry N.A., Lazebnik Y. Caspases: enemies within. Science 281: 1312, 1998. [DOI] [PubMed] [Google Scholar]
  • 7. Green D.R., Reed J.C. Mitochondria and apoptosis. Science 281:1309, 1998. [DOI] [PubMed] [Google Scholar]
  • 8. Lieberthal W., Menza S.A., Levine J.S. Graded ATP depletion can cause necrosis or apoptosis of cultured mouse proximal tubular cells. Am J Physiol 274:F315, 1998. [DOI] [PubMed] [Google Scholar]
  • 9. Mooney A., Jobson T., Bacon R., Kitamura M., Savill J., Cytokines promote glomerular mesangial cell survival in vitro by stimulus‐dependent inhibition of apoptosis. J Immunol 159:3949, 1997. [PubMed] [Google Scholar]
  • 10. Mooney A., Jackson K., Bacon R., Streuli C., Edwards G., Bassuk J., Savill J. Type IV Collagen and Laminin Regulate Glomerular Mesangial Cell Susceptibility to Apoptosis Via beta(1) Integrin‐ Mediated Survival Signals. Am J Pathol 155:599, 1999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11. Ortiz A., Gonzalez‐Cuadrado S., Lorz C., Garcia del Moral R., O'Valle F., Egido J. Cytokines and Fas regulate apoptosis in murine renal interstitial fibroblasts. J Am Soc Nephrol 8:1845, 1997. [DOI] [PubMed] [Google Scholar]
  • 12. Ortiz A., Lorz C., Egido J. New kids in the block: the role of FasL and Fas in kidney damage. J Nephrol 12:150, 1999. [PubMed] [Google Scholar]
  • 13. Lorz C., Ortiz A., Justo P., González‐Cuadrado S., Duque N., Gömez‐Guerrero C., Egido J. Proapoptotic Fas ligand is expressed by normal kidney tubular epithelium and injured glomeruli. J Am Soc Nephrol 11: 1266, 2000. [DOI] [PubMed] [Google Scholar]
  • 14. Schelling J.R., Nkemere N., Kopp J.B., Cleveland R.P. Fas‐dependent fratricidal apoptosis is a mechanism of tubular epithelial cell deletion in chronic renal failure. Lab Invest 78:813, 1998. [PubMed] [Google Scholar]
  • 15. Conaldi P.G, Biancone L., Bottelli A., Wade‐Evans A., Racusen L.C, Boccellino M., Orlandi V., Serra C., Camussi G., Toniolo A. HIV‐1 kills renal tubular epithelial cells in vitro by triggering an apoptotic pathway involving caspase activation and fas upregulation. J Clin Invest 102:2041, 1998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16. González‐Cuadrado S., Löpez‐Armada M.J., Gömez‐Guerrero C., Subirá D., Ortiz‐González A., Neilson E.G., Egido J., Ortiz A. Anti‐Fas antibodies induce cytolysis and apoptosis in cultured human mesangial cells. Kidney Int 49:1064, 1996. [DOI] [PubMed] [Google Scholar]
  • 17. Ortiz‐Arduan A., Danoff T.M., Kalluri R., González‐Cuadrado S., Karp S.L., Elkon K., Egido J., Neilson E.G. Regulation of Fas and Fas ligand expression in cultured murine renal cells and in the kidney during endotoxemia. Am J Physiol 241:F1193, 1996. [DOI] [PubMed] [Google Scholar]
  • 18. González‐Cuadrado S., Lorz C., García del Moral R., O'Valle F., Alonso C., Ramiro F., Ortiz‐González A., Egido J., Ortiz A. Agonistic anti‐Fas antibodies induce glomerular cell apoptosis in mice in vivo . Kidney Int 51:1739, 1997. [DOI] [PubMed] [Google Scholar]
  • 19. Guijarro C., Blanco‐Colío L.M., Ortego M., Alonso C., Ortiz A., Plaza J.J., Díaz C., Hernández G., Egido J. 3‐Hydroxy‐3‐methylglutaryl coenzyme A reductase and isoprenylation inhibitors induce apoptosis of vascular smooth muscle cells in culture. Circ Res 83:490, 1998. [DOI] [PubMed] [Google Scholar]
  • 20. Aravind L., Dixit V.M., Koonin E.V. Apoptotic Molecular Machinery: Vastly Increased Complexity in Vertebrates Revealed by Genome Comparisons. Science 291:1279, 2001. [DOI] [PubMed] [Google Scholar]
  • 21. Saikumar P., Dong Z., Patel Y., Hall K., Hopfer U., Weinberg J.M., Venkatachalam M.A. Role of hypoxia‐induced Bax translocation and cytochrome c release in reoxygenation injury. Oncogene 17:3401, 1998. [DOI] [PubMed] [Google Scholar]
  • 22. Sandau K., Pfeilschifter J., Brune B. Nitric oxide and superoxide induced p53 and Bax accumulation during mesangial cell apoptosis. Kidney Int 52:378, 1997. [DOI] [PubMed] [Google Scholar]
  • 23. Ortiz A., Lorz C., Catalβn M.P., Danoff T.M., Yamasaki Y., Egido J., Neilson E.G. Expression of apoptosis regulatory proteins in tubular epithelium stressed in culture or following acute renal failure. Kidney Int 57:969, 2000. [DOI] [PubMed] [Google Scholar]
  • 24. Ng F.W., Nguyen M., Kwan T., Branton P.E., Nicholson D.W., Cromlish J.A., Shore G.C. p28 Bap31, a Bcl‐2/Bcl‐XL‐ and procaspase‐8‐ associated protein in the endoplasmic reticulum. J Cell Biol 139:327, 1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25. Hacki J., Egger L., Monney L., Conus S., Rosse T., Fellay I, Borner C Apoptotic crosstalk between the endoplasmic reticulum and mitochondria controlled by Bcl‐2. Oncogene 19:2286, 2000. [DOI] [PubMed] [Google Scholar]
  • 26. Nakagawa T., Zhu H., Morishima N., Li E., Xu J., Yankner B.A., Yuan J. Caspase‐12 mediates endoplasmic‐reticulum‐specific apoptosis and cytotoxicity by amyloid‐beta. Nature 403:98, 2000. [DOI] [PubMed] [Google Scholar]
  • 27. Nakagawa T., Yuan J. Cross‐talk between two cysteine protease families. Activation of caspase‐ 12 by calpain in apoptosis. J Cell Biol 150:887, 2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 28. Ortiz A., Ziyadeh F.N., Neilson E.G. Expression of apoptosis‐regulatory genes in renal proximal tubular epithelial cells exposed to high ambient glucose and in diabetic kidneys. J Invest Med 45:50, 1997. [PubMed] [Google Scholar]
  • 29. Sugiyama H., Savill J.S., Kitamura M., Zhao L., Stylianou E. Selective Sensitization to Tumor Necrosis Factor‐alpha‐induced Apoptosis by Blockade of NF‐kappaB in Primary Glomerular Mesangial Cells. J Biol Chem 274:19532, 1999. [DOI] [PubMed] [Google Scholar]
  • 30. Sato T., van Dixhoorn M.G., Schroeijers W.E., Huizinga T.W., Reutelingsperger C.P., van Es L.A., Daha M.R. Apoptosis of cultured rat glomerular mesangial cells induced by IgG2a monoclonal anti‐Thy‐1 antibodies. Kidney Int 49:403, 1996. [DOI] [PubMed] [Google Scholar]
  • 31. Shimizu A., Yamanaka N. Apoptosis and cell desquamation in repair process of ischemic tubular necrosis. Virchows Arch B Cell Pathol Incl Mol Pathol 64:171, 1993. [DOI] [PubMed] [Google Scholar]
  • 32. Olsen T.S., Olsen H.S., Hansen H.E. Tubular ultrastructure in acute renal failure in man: epithelial necrosis and regeneration. Virchows Arch A Pathol Anat Histopathol 406:75, 1985. [DOI] [PubMed] [Google Scholar]
  • 33. Shimizu A., Kitamura H., Masuda Y., Ishizaki M., Sugisaki Y., Yamanaka N. Rare glomerular capillary regeneration and subsequent capillary regression with endothelial cell apoptosis in progressive glomerulonephritis. Am J Pathol 151:1231, 1997. [PMC free article] [PubMed] [Google Scholar]
  • 34. Yang B., Johnson T.S., Thomas G.L., Watson P.F., Wagner B., Skill N.J., Haylor J.L., Nahas A.M. Expression of Apoptosis‐Related Genes and Proteins in Experimental Chronic Renal Scarring. J Am Soc Nephrol 12:275, 2001. [DOI] [PubMed] [Google Scholar]
  • 35. Thomas M.E., Brunskill N.J., Harris K.P., Bailey E., Pringle J.H., Furness P.N., Walls J. Proteinuria induces tubular cell turnover: Apotential mechanism for tubular atrophy. Kidney Int 55:890, 1999. [DOI] [PubMed] [Google Scholar]
  • 36. Ortiz A. Renal cell loss through cell suicide. Kidney Int 58:467, 2000. [DOI] [PubMed] [Google Scholar]
  • 37. Daemen M.A., Van't Veer C., Denecker G., Heemskerk V.H., Wolfs T.G., Clauss M., Vandenabeele P., Buurman W.A. Inhibition of apoptosis induced by ischemia‐reperfusion prevents inflammation. J Clin Invest 104:541, 1999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 38. Basile D.P., Liapis H., Hammerman M.R. Expression of bcl‐2 and bax in regenerating rat renal tubules following ischemic injury. Am J Physiol 272:F640, 1997. [DOI] [PubMed] [Google Scholar]
  • 39. Sharma V.K., Bologa R.M., Li B., Xu G.P., Lagman M., Hiscock W., Mouradian J., Wang J., Serur D., Rao V.K., Suthanthiran M. Molecular executors of cell death‐differential intrarenal expression of Fas ligand, Fas, granzyme B, and perforin during acute and/or chronic rejection of human renal allografts. Transplantation 62:1860.1996. [DOI] [PubMed] [Google Scholar]
  • 40. Murcia N.S., Sweeney W.E. Jr., Avner D.E. New insights into the molecular pathophysiology of polycystic kidney disease. Kidney Int 55:1187, 1999. [DOI] [PubMed] [Google Scholar]
  • 41. Boletta A., Qian F., Onuchic L.F., Bhunia A.K., Phakdeekitcharoen B., Hanaoka K., Guggino W., Monaco L., Germino G.G. Polycystin‐1, the gene product of PKD1, induces resistance to apoptosis and spontaneous tubulogenesis in MDCK cells. Mol Cell 6: 1267, 2000. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Cellular and Molecular Medicine are provided here courtesy of Blackwell Publishing

RESOURCES